Swietenia macrophylla is a large deciduous tree that mainly grows in open rain forests. Its seeds reportedly have many medical efficacies, such as antidiabetic properties and antioxidative effects. This study used ultrasound-assisted extraction (UAE) and Central Composite Design (CCD) Response Surface Methodology (RSM) to optimise the oil yield extracted from S. macrophylla seed. The properties of the extracted S. macrophylla seed oil, namely antioxidant activity and bioactive compounds, were also examined. For the CCD RSM, the seed oil yield was set as the response while the parameters for optimization were solid-to-solvent (SS) ratio (1:3, 1:4, and 1:5), amplitude (70 %, 80 %, and 90 %), and extraction time (5 min, 10 min, and 15 min). The optimum oil yield extracted via UAE was then subjected to several analyses. First, the oil's DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging activity was analysed to determine antioxidant activity. Then, Gas chromatography–Mass spectrometry (GC-MS) analysis was used to evaluate the oil's bioactive compounds (methyl ester fatty acids). The UAE method extracted the optimum yield (27.68 ± 0.3 wt%) of S. macrophylla seed oil under the following conditions: 1:4.5 S/S ratio, 90 % amplitude, and 14.4 min extraction time. The analysis of antioxidant activity revealed a DPPH radical scavenging activity of 87.96 ± 0.04 %. The GC-MS analysis revealed several fatty acids in the oil, including arachidonic acids, stearic acid, palmitic acid, oleic acid, and linoleic acid. This study shows that UAE is a promising method for extracting S. macrophylla seed oil and that S. macrophylla is a potential oral hypoglycaemic agent that could be used for pharmaceutical applications.